U.S. patent application number 11/969085 was filed with the patent office on 2008-07-03 for devices and methods for injection of multiple-component therapies.
This patent application is currently assigned to Medtronic Vascular, Inc.. Invention is credited to Mario Maciel, Asha Nayak.
Application Number | 20080161757 11/969085 |
Document ID | / |
Family ID | 39585018 |
Filed Date | 2008-07-03 |
United States Patent
Application |
20080161757 |
Kind Code |
A1 |
Nayak; Asha ; et
al. |
July 3, 2008 |
Devices and Methods for Injection of Multiple-Component
Therapies
Abstract
Devices and methods for injecting or otherwise delivering
multiple-component therapies to human or animal subjects. Devices
having injectors (e.g., syringes) attached to biaxial or coaxial
injection cannula(s) are used to deliver multiple components of a
particular therapy such that those components become combined
shortly before or upon exiting the injection cannula(s). In some
embodiments, the injector devices of the present invention may
include a first set of finger grips at a first location and a
second set of finger grips at a second location. Also, in some
embodiments, the injector devices of the present invention may
include depth slops for controlling the depth within tissue at
which the therapeutic substance is delivered. Also, in some
embodiments, the injector devices of the present invention may
include refill manifolds with attached syringes or other reservoirs
containing the component substances to facilitate refilling of the
injectors.
Inventors: |
Nayak; Asha; (Menlo Park,
CA) ; Maciel; Mario; (Pinon Hills, CA) |
Correspondence
Address: |
MEDTRONIC VASCULAR, INC.;IP LEGAL DEPARTMENT
3576 UNOCAL PLACE
SANTA ROSA
CA
95403
US
|
Assignee: |
Medtronic Vascular, Inc.
Santa Rosa
CA
|
Family ID: |
39585018 |
Appl. No.: |
11/969085 |
Filed: |
January 3, 2008 |
Related U.S. Patent Documents
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Application
Number |
Filing Date |
Patent Number |
|
|
60878527 |
Jan 3, 2007 |
|
|
|
Current U.S.
Class: |
604/82 |
Current CPC
Class: |
A61M 5/44 20130101; A61M
5/284 20130101; A61M 2205/3606 20130101; A61B 2017/00495 20130101;
A61M 5/3295 20130101; A61M 5/445 20130101; A61M 5/1782 20130101;
A61M 5/3137 20130101; A61B 2018/00392 20130101; A61M 5/204
20130101; A61B 17/3478 20130101; A61M 2205/3646 20130101; A61B
2017/00247 20130101; A61M 5/19 20130101; A61M 2205/3626 20130101;
A61M 5/46 20130101; A61M 5/32 20130101; A61M 2005/3201 20130101;
A61M 2205/3633 20130101; A61M 5/3294 20130101; A61M 2005/3128
20130101 |
Class at
Publication: |
604/82 |
International
Class: |
A61M 37/00 20060101
A61M037/00 |
Claims
1. A device for administering a plurality of component substances
into or onto the body of a human or animal subject such that the
component substances become combined to produce a resultant
component mixture or reaction product that directly or indirectly
results in some therapeutic, diagnostic or cosmetic benefit, said
device comprising: a manifold having a first component substance
flow channel and a second component substance flow channel; a first
injector connectable to the manifold and usable to inject a first
component substance into the first component substance flow channel
of the manifold; a second injector connectable to the manifold and
usable to inject a second component substance into the second
component substance flow channel of the manifold; an injector
cannula assembly comprising; an outer tube that has an outer tube
lumen and a distal opening, said outer tube being connected to the
first component substance flow channel of the manifold such that
the first component substance will flow through the outer tube
lumen; and an inner tube that has an inner tube lumen and a distal
opening, said inner tube being connected to the second component
substance flow channel of the manifold such that the second
component substance will flow therefrom into the inner tube lumen
and out of the distal opening of the inner tube; and wherein at
least a portion of the inner tube extends through at least a
portion of the outer tube lumen such that the second component
substance becomes combined with the first component substance
thereby forming a resultant component substance mixture or reaction
product.
2. A device according to claim 1 wherein the distal opening of the
inner tube is located within the outer tube lumen such that the
first and second component substances become combined within the
outer tube lumen.
3. A device according to claim 1 wherein the distal end opening of
the inner tube is located flush with or outside of the distal
opening of the outer tube such that the first and second component
substances become combined after exiting the distal openings of the
inner and outer tubes.
4. A device according to claim 1 wherein a portion of the inner
tube is substantially coaxially disposed within the outer tube
lumen.
5. A device according to claim 1 further comprising a handle that
facilitates holding of the device by a human operator, the handle
being configured to hold the first and second injectors; and the
handle further comprises a depressible member that, when depressed,
causes substantially simultaneous injection of the first and second
component substances from the first and second injectors.
6. A device according to claim 5 wherein the handle further
comprises finger grips for receiving the operator's fingers while
the operator's thumb is used to depress the depressible member and
the handle is configured such that an operator can use the device
with a one hand.
7. A system according to claim 5 wherein the first and second
injectors have plungers which may be depressed to cause injection
of the first and second component substances and wherein the
depressible member engages the plungers of the first and second
injectors and is usable to simultaneously depress those plungers at
substantially the same rate.
8. A system according to claim 1 wherein the first injector and
second injector differ in size.
9. A system according to claim 8 wherein the ratio of the volumes
of the first injector and the second injector is approximately ten
to one.
10. A device according to claim 1 further comprising: a first fill
reservoir for containment of a quantity of the first component
substance and a second fill reservoir for containment of a quantity
of the second component substance; the first fill reservoir being
connected to the first injector and the second fill reservoir being
connected to the second injector such that the first injector may
be loaded with a quantity of the first component substance from the
first fill reservoir and the second injector may be loaded with a
quantity of the second component substance from the second fill
reservoir, without requiring detachment of the first or second
injectors from the manifold.
11. A device according to claim 10 further comprising first and
second valves, each of said first and second valves being movable
between i) a first position whereby it allows a quantity of a
component substance to flow from a fill reservoir into an injector
and ii) a second position whereby the component substance may be
injected from that injector through the manifold and through the
injector cannula without backflowing into the fill reservoir.
12. A device according to claim 1 further comprising apparatus for
controlling or maintaining the temperature of at least one
component substance.
13. A device according to claim 12 wherein the device includes at
least one fill reservoir from which a component substance flows
into a component injector and wherein the apparatus for controlling
or maintaining the temperature of at least one component substance
operates to control or maintain the temperature of a component
substance while it is contained in the at least one fill
reservoir.
14. A device according to claim 1 further comprising apparatus for
agitating at least one component substance.
15. A device according to claim 14 wherein the device includes at
least one fill reservoir from which a component substance flows
into a component injector and wherein the apparatus for agitating
at least one component substance operates to agitate a component
substance while contained in the at least one fill reservoir.
16. A device according to claim 1 wherein the injector cannula has
a sharp tissue-penetrating distal end.
17. A device according to claim 1 further comprising a depth stop
for limiting the depth to which the injector cannula may be
advanced into tissue.
18. An injector device comprising: At least one injector having a
barrel into which a flowable substance may be loaded, an outlet
opening and a plunger that may be depressed by the thumb of a user
to cause a substance that has been loaded into the barrel to be
expelled out of the outlet opening; a first set of finger grips at
a first location; and a second set of finger grips at a second
location.
19. An injector device according to claim 18 wherein said at least
one injector comprises: a first injector having a barrel into which
a first substance may be loaded, a first outlet opening and a first
plunger that, when depressed, causes a first substance that has
been loaded into the barrel of the first injector to be expelled
out of the outlet opening of the first injector; a second injector
having a barrel into which a second substance may be loaded, a
second outlet opening and a second plunger that, when depressed,
causes a second substance that has been loaded into the barrel of
the second injector to be expelled out of the outlet opening of the
second injector; a thumb-depressible member that engages both the
first and second plungers so as to depress both the first and
second plungers at substantially the same rate; a manifold
connected to the first and second injectors, said manifold having a
first substance flow channel into which the first substance flows
from the first injector and a second substance flow channel into
which the second substance flows from the second injector; and at
least one cannula attached to the manifold.
20. A device according to claim 19 wherein said at least one
cannula comprises a first cannula lumen through which the first
substance flows and a second cannula lumen through which the second
substance flows, and the first cannula lumen and the second cannula
lumen are in biaxial relation to one another.
21. A device according to claim 19 wherein said at least one
cannula comprises a cannula assembly that includes; an outer tube
that has an outer tube lumen and a distal opening, said outer tube
being connected to the first substance flow channel of the manifold
such that the first substance will flow through the outer tube
lumen; and an inner tube that has an inner tube lumen and a distal
opening, said inner tube being connected to the second substance
flow channel of the manifold such that the second substance will
flow therefrom into the inner tube lumen and out of the distal
opening of the inner tube; and wherein at least a portion of the
inner tube extends through at least a portion of the outer tube
lumen such that the second substance becomes combined with the
first substance thereby forming a resultant substance mixture or
reaction product.
22. A device according to claim 21 wherein a portion of the inner
tube is substantially coaxially disposed within the outer tube
lumen.
23. A device according to claim 18 wherein said at least one
injector comprises a syringe.
24. A device according to claim 19 further comprising: a first fill
reservoir for containment of a quantity of the first substance and
a second fill reservoir for containment of a quantity of the second
substance, the first fill reservoir being connected to the first
injector and the second fill reservoir being connected to the
second injector such that the first injector may be loaded with a
quantity of the first substance from the first fill reservoir and
the second injector may be loaded with a quantity of the second
substance from the second fill reservoir, without requiring
detachment of the first or second injectors from the manifold; and
a first valve and a second valve, each of said first and second
valves being movable between i) a first position whereby it allows
a quantity of a substance to flow from a fill reservoir into an
injector and ii) a second position whereby the substance may be
injected from that injector without backflowing into the fill
reservoir.
25. A device according to claim 24 wherein the first and second
fill reservoirs comprise syringes.
26. A device according to claim 24 further comprising apparatus for
controlling or maintaining the temperature of at least one of the
substances while the at least one substance is contained in at
least one of the first fill reservoir or the second fill
reservoir.
27. A device according to claim 24 further comprising apparatus for
agitating at least one of the substances while the at least one
substance is contained in at least one of the first fill reservoir
or the second fill reservoir.
28. A device according to claim 19 wherein said at least one
cannula has a sharp tissue-penetrating distal end and a depth stop
for limiting the depth to which the cannula may be advanced into
tissue.
Description
RELATED APPLICATION
[0001] This patent application claims priority to U.S. Provisional
Patent Application No. 60/878527 filed Jan. 3, 2007.
FIELD OF THE INVENTION
[0002] The present invention relates generally to medical devices
and methods, and more particularly to devices and methods for
injecting or otherwise delivering multiple-component therapies to
human or animal subjects.
BACKGROUND
[0003] It is sometimes desirable to deliver (e.g., inject, infuse,
apply, etc) two or more chemical substances to a desired location
within the body of a human or animal subject such that the
substances become combined or mixed shortly before, during or
shortly after delivery into the body. For example, some therapies
involve the administration of two or more component substances
(e.g., chemical compounds, solutions, suspensions, biologics,
cells, reactants, etc.) such that those substances react or
otherwise interact with each other to form a resultant mixture or
reaction product that directly or indirectly results in some
therapeutic, diagnostic or cosmetic benefit (generally referred to
herein as "Multiple-Component Therapies"). In some cases, it is
important for the component substances to be combined or mixed
immediately before, during or after delivery. This is the case, for
example, when mixing or combining of the component substances too
long before delivery would result in an increase in viscosity or
solidification process that would render the product incapable of
passing through an intended delivery cannula or needle or where the
product has a very short half life and would loose activity before
reaching its intended in vivo destination.
[0004] One Multiple Component Therapy is known as platelet gel
(PG). In this therapy, a platelet-containing component (e.g.,
platelet rich plasma (PRP)) is combined with a thrombin-containing
component (e.g, a thrombin solution) immediately before, during or
after injection into the myocardium at one or more location(s)
within or near an infarct or other myocardial injury. The
platelet-containing component (e.g., PRP) combines with the
thrombin-containing component and forms a platelet gel (PG) which
causes the desired therapeutic effect. Such PG is formed when
components (such as fibrinogen) contained in the
platelet-containing component are activated by thrombin contained
in the thrombin-containing component. Autologous PRP can be
obtained from the subject's own blood, thereby significantly
reducing the risk of adverse reactions or infection. When
autologous PRP is used as the platelet-containing component, the
resultant PG is referred to as autologous platelet gel (APG). The
addition of thrombin to platelet-containing plasma products such as
PRP is described in detail in U.S. Pat. No. 6,444,228, the
disclosure of which is expressly incorporated herein by reference.
PRP has also been used in a variety of orthopedic and other
applications.
[0005] Moreover, the preparation and use of PG and APG for
improving cardiac function and/or preventing deleterious
ventricular remodeling following myocardial infarction or other
injury to the myocardium is being investigated by Medtronic
Vascular, Inc. of Santa Rosa, Calif., as described in parent U.S.
patent application Ser. No. 11/426,219 (published as 2007-0014784)
and in United States Patent Application Publication Nos.
2006/0041242 and 2005/209564, the entire disclosures of which are
expressly incorporated herein by reference. Since it may be
difficult to pass PG or APG through the lumen of a needle, it is
desirable to inject the platelet-containing component and the
thrombin-containing component such that they become mixed
immediately prior to, during or after injection through the needle.
Additionally, injecting the platelet-containing component and the
thrombin-containing component separately or immediately after
mixing may allow the infusate to distribute to a greater area
before fully gelling into the PG or APG, thereby possibly enhancing
the effect of this therapy.
[0006] Other examples of Multiple Component Therapies known in the
prior art include, but are not limited to; multiple component
tissue adhesives and sealants (e.g., Tisseel VH.TM. Fibrin Sealant,
available commercially from Baxter Healthcare Corporation,
Deerfield, Ill.); tissue bulking agents, fillers or polymeric
materials (e.g., hydrogels) that may be formed or expanded in situ
for various therapeutic or cosmetic applications such as tissue
bulking, filling or expanding and various prodrug+activator
combinations.
[0007] The prior art has also included a number of injector
assemblies that may be usable for delivering Multiple Component
Therapies. For example, U.S. Pat. No. 4,823,985 (Grollier, et al.)
describes a dispensing assembly usable for dispensing at least two
constituents such that the constituents become mixed to form a
homogenous product. This dispensing assembly has flexible walls and
at least two compartments, including outlet orifices located
adjacent to one another so that when the outlet orifices are opened
as by cutting, and pressure is applied to the flexible walls,
dispensing and immediate mixing of the constituents will be
effected; the viscosity and volumes of the constituents are
selected to have certain values to enable the dispensing to
properly mix the constituents to form a homogenous product. The
dispensing assemblies described in U.S. Pat. No. 4,823,985
(Grollier et al.) do not include any needle having a tissue
penetrating tip or other means for injecting the constituents into
tissue.
[0008] U.S. Pat. No. 6,936,033 (McIntosh, et al.) describes a
double syringe system for holding a pair of syringes in a manner so
as to accommodate the simultaneous activation of the plunger of
each syringe in order to effect simultaneous delivery of the
contents of each syringe. The delivery system includes a support
member that is positioned between the two syringe bodies. The
elongated support member has resilient, C-shaped clamps on one end
of the support member. The clamps are designed to be removably
clamped onto the applicator so that the syringe barrels will be
held together in a parallel manner. The elongated support member
further comprises finger grips. A plunger connects the two syringe
plungers so that they can also be simultaneously activated. Two
side-by-side cannulas extend from the distal end of the delivery
system and, as the plungers are depressed, the material from one
syringe flows through one cannula and the material from the other
syringe flows through the other cannula. The distal ends of the
cannulas are aligned with each other so that there will be
simultaneous delivery of the separated fluids from both syringes to
the application site. In one embodiment, the side-by-side cannulas
comprise needles of substantially equal length. Each of these
needles bent towards each other so that as the needles approach
their distal ends, they run parallel to each other and touch. The
parallel portions of needles can be joined together with a sleeve,
adhesive, or other methods known in the art. In another embodiment,
the cannulas are formed of flexible lengths of tubing that are cut
off at equivalent lengths and attached at their distal ends,
usually with solvent adhesive. In yet another embodiment, the
delivery system has a delivery tip that comprises a hollowed double
fluid path attached to a single cannula fitting such as that
described in U.S. Pat. No. 5,104,375, which is specifically
incorporated herein by reference. Alternatively, the delivery
system may have spray heads attached to each syringe.
[0009] U.S. Pat. No. 6,942,639 (Baugh et al.) describes a system
for delivering and combining an activated blood component and an
inactivated blood component, which combine to form APG. This system
comprises separate chambers which contain the activated blood
component and the inactivated blood component, respectively. The
first chamber includes an activating agent and a filter (which may
be one and the same) which causes a clot (which forms in the blood
component) to become triturated, thereby isolating thrombin from
the clot. The second chamber stores the inactivated blood component
(e.g., PRP) that, when mixed with thrombin, produces a gel. The
first or second chamber may further contain agents which are
desired to be delivered to a specific site. The design of the
delivery system allows for ease in operation of combining two
agents at a specific time and place.
[0010] United States Published Patent Application 2006/0253082
describes dispensing systems and methods for dispensing platelet
gel or other two component treatments. These dispensing systems
include a handle assembly that is designed to hold two syringes and
thumb plate that is used to depress the plungers of both syringes
simultaneously. The fluids contained in the separate syringes then
flow through separate channels in a manifold and through a tip
assembly. In various embodiments the tip assembly may include
specialized various nozzles that entrain non-atomized flow of a
first fluid in an atomized flow of a second fluid, delivering a
first fluid upstream from a second fluid, delivering a first fluid
and a second fluid with re-shapeable malleable tubes, delivering
first and second fluids with releasable connectors maintained by a
handle assembly.
[0011] There remains a need for the development of new devices and
methods for injecting platelet gel or other Multiple Component
Therapies to selected locations within the bodies of human or
animal subjects such that the component substances become mixed or
combined immediately before, during or after delivery into or onto
the body of the subject.
SUMMARY OF THE INVENTION
[0012] The present invention provides new devices and methods for
administering Multiple Component Therapies such that the component
substances become combined immediately before, during or after
delivery into or onto the body of a human or animal subject.
[0013] In accordance with the invention, there is provided a device
for administering a plurality of component substances into or onto
the body of a human or animal subject such that the component
substances become combined to produce a resultant component mixture
or reaction product that directly or indirectly results in some
therapeutic, diagnostic or cosmetic benefit. Such device generally
comprises a) a manifold having a first component substance flow
channel and a second component substance flow channel; b) a first
injector connectable to the manifold and usable to inject a first
component substance into the first component substance flow channel
of the manifold; c) a second injector connectable to the manifold
and usable to inject a second component substance into the second
component substance flow channel of the manifold and d) an injector
cannula assembly comprising i) an outer tube that has an outer tube
lumen and a distal opening, said outer tube being connected to the
first component substance flow channel of the manifold such that
the first component substance will flow through the outer tube
lumen and ii) an inner tube that has an inner tube lumen and a
distal opening, said inner tube being connected to the second
component substance flow channel of the manifold such that the
second component substance will flow therefrom into the inner tube
lumen and out of the distal opening of the inner tube. At least a
portion of the inner tube extends through at least a portion of the
outer tube lumen such that the second component substance flowing
out of the distal opening of the inner tube becomes combined with
the first component substance that flows through the lumen of the
outer tube thereby forming a resultant component substance mixture
or reaction product.
[0014] Further in accordance with the present invention, there is
provided a method for administering a plurality of component
substances into or onto the body of a human or animal subject such
that the component substances become combined to produce a
resultant mixture or reaction product that directly or indirectly
results in some therapeutic, diagnostic or cosmetic benefit. Such
method generally comprises the steps of: a) providing a device
which comprises i) a manifold having a first component substance
flow channel and a second component substance flow channel, ii) a
first injector connectable to the manifold and usable to inject a
first component substance into the first component substance flow
channel of the manifold, iii) a second injector connectable to the
manifold and usable to inject a second component substance into the
second component substance flow channel of the manifold and iv) an
injector cannula assembly that includes an outer tube that has an
outer tube lumen and a distal opening, said outer tube being
connected to the first component substance flow channel of the
manifold such that the first component substance will flow through
the outer tube lumen and an inner tube that has an inner tube lumen
and a distal opening, said inner tube being connected to the second
component substance flow channel of the manifold such that the
second component substance will flow therefrom into the inner tube
lumen and out of the distal opening of the inner tube, wherein at
least a portion of the inner tube extends through at least a
portion of the outer tube lumen such that the second component
substance flowing out of the distal opening of the inner tube
becomes combined with the first component substance that flows
through the lumen of the outer tube thereby forming a resultant
component substance mixture or reaction product; b) attaching
injectors to the manifold, c) positioning the injector cannula at a
desired location within or on the subject's body and d) using the
injectors to inject component substances through the manifold and
through the at least one injector cannula such that the resultant
component substance mixture or reaction product is deposited at a
desired location in or on the subject's body.
[0015] Still further in accordance with the present invention,
there is provided an injector device which generally comprises a)
at least one injector having a barrel into which a flowable
substance may be loaded, an outlet opening and a plunger that may
be depressed by the thumb of a user to cause a substance that has
been loaded into the barrel to be expelled out of the outlet
opening, b) a first set of finger grips at a first location and c)
a second set of finger grips at a second location.
[0016] Still further in accordance with the present invention,
there is provided a method for administering at least one substance
into or onto the body of a human or animal subject. Such method
generally comprises the steps of a) providing a device which
comprises i) at least one injector having a barrel into which a
substance may be loaded, an outlet opening and a plunger that may
be depressed to cause a substance that has been loaded into the
barrel to be expelled out of the outlet opening, ii) a first set of
finger grips at a first location and iii) a second set of finger
grips at a second location, b) loading a substance into the barrel,
c) selecting either the first set of finger grips or the second set
of finger grips, d) placing fingers of one hand under the finger
grips selected in Step B, e) placing the thumb of the same hand in
a position to depress the plunger and f) using the thumb to depress
the plunger thereby expelling at least some of the substance from
the barrel and out of the outlet opening.
[0017] Further or alternative elements, aspects, objects and
advantages of the present invention will be understood by those of
skill in the art upon studying of the accompanying drawings and
reading of the detailed description and examples set forth
below.
BRIEF DESCRIPTION OF THE DRAWINGS
[0018] FIG. 1A is a top perspective view of one embodiment of a
Multiple Component Therapy delivery device of the present
invention.
[0019] FIG. 1B is an enlarged view of a distal portion of the
device of FIG. 1A
[0020] FIG. 2 is an exploded view of the device of FIG. 1A.
[0021] FIG. 2A is an enlarged side view of the coaxial injector
cannula of the device of FIG. 1A.
[0022] FIG. 2B is an enlarged side view of an alternative biaxial
injector cannula that may be incorporated in the device of FIG.
1A.
[0023] FIG. 3 is a diagram showing a sagittal section of a human
heart with a device of the present invention being used to inject
APG into a myocardial infarct zone located the anterior wall of the
left ventricle near the apex of the heart.
[0024] FIG. 3A is an enlarged view of section 3A of FIG. 3.
[0025] FIG. 4 is a diagram of a human heart with an infarct of the
anterior left ventricular wall showing one example of locations at
which APG can be injected into the myocardium to treat impaired
myocardial function resulting from the infarct.
[0026] FIG. 5 is a schematic, cross sectional diagram of a portion
of a human heart showing a device of the present invention being
used to inject deposits of a Multiple Component Therapy at selected
locations within a ventricle wall.
[0027] FIG. 6 shows an embodiment of a fill reservoir portion of
the device of FIG. 1A including optional temperature control and
mixing devices.
[0028] FIG. 7 is an exploded view of an optional depth stop device
that may be used to control the depth at which a substance is
delivered into tissue using the devices and methods of the present
invention.
DETAILED DESCRIPTION AND EXAMPLES
[0029] The following detailed description and the accompanying
drawings are intended to describe some, but not necessarily all,
examples or embodiments of the invention. The contents of this
detailed description and accompanying drawings do not limit the
scope of the invention in any way.
[0030] With reference to FIGS. 1A-2B, one embodiment of a Multiple
Component Therapy delivery device 10 of the present invention
generally comprises a manifold 12 having a coaxial injector cannula
14 extending distally therefrom, an optional fill reservoir
assembly 40 that is attached to the manifold 12, component
substance injectors (e.g., syringes) 16, 18 (or alternatively other
types of injectors for infusing or injecting the component
substances) and a handle/injection control assembly 20. The
manifold 12 may be formed of molded plastic or otherwise
constructed of materials that are compatible with the component
substances that are to be infused therethrough. The coaxial
injector cannula 14 of this embodiment may, in some embodiments,
have a sharp distal end suitable for advancement through tissues of
the body or may have blunt distal end(s) suitable, for example, for
topical application or for advancement into the body through an
existing opening (e.g., a natural or man made orifice, opening,
incision, port, introducer, trocar or the like).
[0031] One use that is contemplated for the current invention is to
deliver multi component therapeutic substances into a heart. Access
to the heart can be achieved via an open chest surgical procedure,
through the walls of the chest during a minimally invasive surgical
procedure, or via a percutaneous injection while using suitable
imaging techniques to ensure delivery to the appropriate
location.
[0032] Those of skill in the art will appreciate that the device 10
may be used to deliver a variety of Multiple Component Therapies by
any desired routes of administration, including but not limited to
topical routes (e.g., epicutaneous, epimucosal, epiconjunctival or
by delivery onto internal body surfaces through nasal, oral,
rectal, vaginal, urethral or other administration), enteral routes
(oral, rectal, by gastric tube or other introduction for absorption
via the gastrointestinal tract) and/or parenteral routes (e.g.,
intramuscular, intravenous, intraarterial, intrathecal,
subcutaneous, intraosseous, intradermal, intraperitoneal,
intravitreal, intracardiac, etc.)
[0033] In use, the device 10 may be use to inject or deliver a
desired Multiple Component Therapy. In the particular embodiment
shown in FIGS. 1A-2A, the component substances are expelled from
the component injectors 16, 18 and flow through separate flow
channels 28, 30 within the manifold 12. As may be appreciated from
the enlarged views of FIGS. 2A and 2B, in embodiments which
incorporate the coaxial injection cannula 14, the first component
substance flows from one channel 28 of manifold 12 into a first
injection cannula 70 and the second component substance flows from
the other channel 30 of the manifold 12 into a second injection
cannula 72. In the depicted embodiment, the first injection cannula
70 is shorter than the second injection cannula 72. For example, in
some embodiments, the first injection cannula may extend
approximately 3 mm out of the manifold 12 and the second injection
cannula 72 may extend out of the manifold 12. The first and second
injection cannulas 70, 72 may be formed or any suitable material,
such as stainless steel hypotube of a size that is appropriate for
the intended application. For example, in devices 10 intended for
use in injecting APG into myocardial tissue, a stainless steel
hypotube of about 24 gauge to about 28 gauge and typically about 26
gauge, may be used. A side opening 77 is formed in the second
injection cannula 72 some distance distal to the end of the first
injector cannula 70. A tube 76, such as a flexible plastic tube, is
connected to the first injection cannula and extends through side
opening 77 and into the lumen 79 of second injection cannula 72, as
shown in FIG. 2A. The tube 76 extends distally through the lumen 79
of the second injector cannula 72 to a position where the distal
end 78 of the tube 76 is a desired distance D.sub.1 from the open
distal end 74 of the second injector cannula 72. The tube 76 has an
outer diameter that is smaller than the inner diameter of the
second injection cannula 72. The first component substance flows
from the first injector cannula 70, through tube 76 and out of the
distal end of tube 78. The second component substance flows through
the lumen 79 of the second injector cannula 72 and around the
portion of tube 76 that resides within lumen 79 such that the first
and second component substances become combined to form a resultant
component mixture or reaction product.
[0034] This distance D.sub.1 between the distal end 78 of the tube
76 and the distal end 74 of the second injector cannula 72 may
vary, depending on the type of Multiple Component Therapy being
delivered. For example, in some embodiments the distal end 78 of
the tube 76 may be substantially flush with the distal end 76 of
second injector cannula 72 (i.e., D.sub.1=0) such that the first
and second component substances remain separate and do not become
mixed until they exit the distal end 74 of the second injection
cannula 72. In other embodiments, the distal end 78 of the tube 76
may be some distance proximal to the distal end 76 of second
injector cannula 72 (i.e., D.sub.1>0) such that the first and
second component substances become mixed while in the lumen 79 of
the second injection cannula 72 and the resultant component mixture
or reaction product will be formed before it flows out of the
distal end 74 of the second injection cannula 72.
[0035] In at least one embodiment that is not depicted, the distal
end of the tube that comprises the first injection cannula extends
beyond the distal end of the second injection cannula and the
distal ends of both the first injection cannula and the second
injection cannula are beveled. In such an embodiment, the tube that
comprises the first injection cannula is made from a material that
will provide the necessary rigidity for delivering an injectate
into a desired tissue (e.g. a stainless steel hypotube). This
embodiment allows delivery of separate components at different
depths in the tissue relative to each other. In some instances
where separate components are delivered to different depths
relative to each other, the components combine with each other in
the tissue after the injection device has been withdrawn.
[0036] In general, this coaxial injector 14 embodiment may be
useful for delivering Multiple Component Therapies where it is
desired to keep the component substances separate until they exit
the injector or just prior to their exit from the injector. Such
may be desirable in situations where the resultant component
mixture or reaction product undergoes a rapid chemical reaction, a
rapid change in state, a rapid increase in viscosity, has a very
short active life or otherwise must be administered immediately or
very shortly after the component substances have become combined or
mixed.
[0037] It will be appreciated by those of skill in the art that the
specific construction of the coaxial injector cannula 14 shown in
the figures is merely an example and other alternative modes of
construction may be employed to achieve the desired result. For
example, in some embodiments, the manifold 12 may be designed such
that the first and second flow channels 28, 30 become merged within
manifold 12 and the resultant component mixture or reaction product
then flows through a single lumen (e.g., a single injection
cannula) that extends from the manifold 12.
[0038] FIG. 2B shows the distal portion of a biaxial injection
cannula 14a wherein a first injection cannula 70a and second
injection cannula 72a extend in side by side fashion. A sharp,
beveled distal end 74a may be formed at the distal ends of these
injection cannulas 70a, 72a. In this embodiment, one component
substance flows through the lumen 71 of the first injection cannula
70a and a second component substance flows through the lumen 79a of
the second injection cannula 72a Such biaxial lumens 71, 79a are
sufficiently close-spaced that, as the separate streams of
component substances flow out of the distal ends of these cannulas
70a, 72a, they will become combined (e.g., they may pool together
within tissue or on a surface of the subject's body) thus resulting
in situ formation of the resultant component combination or
reaction product. In such embodiments, the biaxial lumens may be of
differing or equal lengths. In the particular example shown the
first injection cannula 70a is only slightly shorter than the
second injection cannula 72a due to the nature of the bevel cut at
the distal end 74a. Having a bevel cut at the distal end of the
biaxial injector cannula 14a or coaxial injector cannula 14 may be
useful in applications where it is desired to deliver the Multiple
Component Therapy to a location that is adjacent to one side or the
other of the injection cannula tip, such as within the myocardium
near the apex of the heart when the needle is advanced at an
inferior angle such that the apex is located to one side of the
needle as seen in FIGS. 3 and 3A.
[0039] As shown in FIGS. 1A and 2, when the three way stopcocks
42a, 42b (or other suitable valves) of the optional fill reservoir
assembly 40 are attached to manifold 12 and component injector
syringes 16, 18 as well as fill reservoirs (e.g., syringes that are
larger than the corresponding injector syringes) are attached to
separate side arms of valves such as three way stopcocks 42a, 42b.
These stopcocks 42a, 42b may be alternately placed in a first
position that allows component substance material to be withdrawn
from fill syringe 52 through elbow 46b into delivery syringe 16 and
from fill syringe 54 through elbow 46a into delivery syringe 18.
Thereafter, the stopcocks 42a, 42b may be moved to a second
position that allows the component substances to be injected from
component substance syringes 16, 18, through manifold 12 and
through the delivery cannula(s) or needle(s) 14, 14a. This may be
repeated one or more times, thus allowing the component substance
syringes 16, 18 to be refilled and used to deliver repeated doses
or injections of the Multiple Component Therapy without requiring
that the component substance syringes 16, 18 be removed or detached
from the device 10. It is to be appreciated that, although the
drawings show the use of fill syringes 52, 54 as the fill
reservoirs, various other types of reservoirs may be used instead
of syringes. For example, compliant reservoirs, such as flexible
vessels or plastic bags, may be filled with the component
substances and connected to the appropriate side arms of stopcocks
42a, 42b and may function as fill reservoirs instead of the fill
syringes 52, 54 shown in the drawings.
[0040] The device 10 also may include an optional handle/injection
control assembly 20 which facilitates handling of the device 10 as
well as simultaneous depression and/or withdrawal of the plungers
16a, 18a of component injector syringes 16, 18. The component
injector syringes 16, 18 are mounted in syringe mounting brackets
26 with two sets of finger grips 24a, 24b protruding between the
syringes 16, 18. One set of finger grips 24a is located distal to
the other set of finger grips 24b, thereby allowing users having
different sized hands to select the finger grip set 24a, 24b that
is best suited from them. The thumb pads located on the ends of
syringe plungers 16a, 18a are received in slots formed on a
depressible member such as thumb plate 22. Rods 23 slide back and
forth in bores formed in body member 27. Thus, when filling the
syringes 16, 18, the stopcocks 42a, 42b are placed in their first
positions and the syringe plungers 16a, 18a are simultaneously
retracted by pulling the thumb plate 22 in the proximal direction.
It will be appreciated that, in some embodiments, instead of
including two or more sets of finger grips 24a, 24b at
longitudinally spaced apart locations, a single set of
longitudinally adjustable finger grips 24a may be provided such
that the operator may adjust the position of those finger grips
thereby setting the distance between that adjustable set of finger
grips and the thumb plate 22 to optimize comfort and ease of use
for that operator.
[0041] It will be further appreciated that, in some applications,
both component injector syringes 16, 18 may be of substantially the
same length and/or size while in other applications the component
injector syringes 16, 18 may be of substantially different length
or size. In applications where one of the component injector
syringes 16, 18 is shorter than the other, the shorter syringe may
be attached to the proximal end of an optional spacer 50 (e.g., a
straight male-female Luer fitting) and the distal end of that
spacer 50 may be attached to the adjacent stopcock 42a or 42b. In
this manner, by selecting a spacer 50 of the proper length, the
component injector syringes 16, 18 will be appropriately positioned
such that their plunger thumb pads 16a, 18a will insert into the
respective slots on thumb plate 22 and their plungers 16a, 18a will
advance concurrently with advancement of the thumb plate 22 to
expel the intended amounts of the component substances, despite
differences in the lengths of the component injector syringes 16,
18. Use of this optional spacer 50 may be particularly advantageous
in applications where the intended component substance mix ratio
requires delivery of a comparatively large volume of one component
substance and a comparatively small volume of another component
substance.
[0042] After the component injector syringes 16, 18 have been
filled with the component materials, the stopcocks 42a, 42b are
moved to their second positions. The injector cannula(s) 14,14a
is/are inserted into the subject's body or positioned adjacent to
an area on the subject's body to which the Multiple Component
Therapy is to be delivered. As shown in the drawings, in some
embodiments, the injector cannula(s) 14,14a may have beveled or
otherwise sharp tips capable of penetrating through tissue and the
procedure may involve advancing the injector cannula(s) 14,14a
through tissue to a desired location where the Multiple Component
Therapy is to be delivered. Specific examples of this are shown in
FIGS. 3-5 and are described in detail herebelow.
[0043] Alternatively, for some applications, the injector
cannula(s) 14,14a may have blunt tips. Examples of application
where blunt tipped injector cannula(s) 14,14a may be used include
but are not necessarily limited to those in which the Multiple
Component Therapy is to be delivered topically onto a body surface
or through an existing body orifice or opening (e.g., intranasal,
rectal, vaginal, etc.) such that it is not necessary for the distal
ends of the injector cannula(s) 14,14a to penetrate through
tissue.
[0044] After the injector cannula(s) 14,14a have been positioned at
the desired location, the operator's fingers are inserted under the
selected set of finger grips 24a, 24b and the operator's thumb is
placed on thumb plate 22. Thumb pressure is then applied to advance
thumb plate 22 in the distal direction, thereby depressing syringe
plungers 16a, 16b simultaneously at substantially the same rate.
This causes the component substances to flow through manifold 12
and through the delivery cannula(s) or needle(s) 14 and causes the
resultant combination material to be delivered onto or into the
subject's body as described herein.
[0045] As seen in FIGS. 1A, 1B and 7, an optional depth stop 15,
15a may be formed on, attached to or positioned adjacent the
delivery cannula(s) or needle(s) 14, 14a to limit the depth to
which the delivery cannula(s) or needle(s) 14, 14a may be advanced
into tissue. Such depth stop 15, 15a may comprise an enlarged
diameter area or projections formed on the outer surface(s) of the
delivery cannula(s) or needle(s) 14, 14a or may comprise a separate
device that is attached to the delivery cannula(s) or needle(s) 14,
14a, an example of which is shown in FIG. 7. The depth stop device
15a seen in FIG. 7 comprises an abutment member 90 having an
aperture 92 through which the delivery cannula(s) or needle(s) 14,
14a may be advanced and a tightening member 94, such as a set
screw, which frictionally engages the delivery cannula(s) or
needle(s) 14, 14a and holds the abutment member 90 at the desired
location on the delivery cannula(s) or needle(s) 14, 14a. In this
manner, the delivery cannula(s) or needle(s) 14, 14a may be
advanced into tissue only until the abutment member 90 abuts
against the surface of the tissue (e.g., the epicardial surface of
the heart, organ or other anatomical structure) thereby controlling
the depth at which the substance will be injected.
[0046] In another embodiment of depth stop (not shown) the surface
of the abutment member that makes contact with the surface of the
tissue is beveled. The angle of the bevel can be set at an angle
that will allow the distal tip of the cannula(s) or needle(s) to
penetrate the tissue at a desired angle (for example an injection
toward the apex of a heart).
[0047] It will be appreciated that the devices and methods of this
invention may be used to deliver many types of Multiple Component
Therapies. As seen in FIGS. 3-5, in one particular type of Multiple
Component Therapy, the component substances comprise a
platelet-containing component (e.g., PRP or autologous PRP) and a
thrombin-containing component (e.g., a thrombin solution) and the
resultant combination material is PG or APG. The PG or APG is
delivered to selected sites within the myocardium to deter negative
remodeling of the ventricular wall or to otherwise improve
myocardial function as described in U.S. patent application Ser.
No. 11/426,219 (published as 2007-0014784) and in United States
Published Patent Application Nos. 2006/0041242 and 2005/209564, the
entire disclosures of which are expressly incorporated herein by
reference. This is illustrated in the schematic diagram of FIGS.
3-5 wherein the coaxial injector cannula 14 is shown to be inserted
into myocardial tissue within or near an infarct zone IZ that is
located in the myocardial wall of the left ventricle LV near the
apex AP of the heart. In some applications, a single injection of
the Multiple Component Therapy may be sufficient. In other
applications, the injector cannula 14 may be withdrawn and
reinserted at a number of locations and a deposit 60a, 60b of
APG+thrombin solution will be deposited at each such location
within the myocardium M, without penetrating into the ventricle
adjacent ventricle. The locations at which the deposits 60a, 60b
are deposited may form a pattern within and/or adjacent to an
infarct zone IZ as shown, for example, by deposits 60 in FIG. 4.
Injections may be made into normal, injured, or diseased tissue,
depending on the type of substance being delivered and its intended
effect.
[0048] FIG. 6 shows an optional agitation device 80 and an optional
temperature control device 82 that may, in some embodiments, be
included to agitate (e.g., mix, shake, stir, swirl, move, spin,
etc.) or otherwise prevent settling or separation of the one or
more of the component substances and/or to control the temperature
of one or more of the component substances. Such optional agitation
device 80 and an optional temperature control device 82 will
typically be attached or connected to an optional fill reservoir
(e.g., fill syringes 52 and/or 54) but, in some cases, may be
attached or connected to the component injectors (e.g., component
injector syringes 16, 18). For example, in cases where the optional
fill syringe 52 contains a thrombin containing component such as
thrombin solution used in the delivery of PG or APG therapy, it may
be desired to maintain the thrombin containing component at a
desired temperature, for example at below room temperature. To
accomplish this, an insulation material and/or a coolant device 82
(e.g., ice pack, endothermic reaction coolant, refrigeration unit,
thermoelectric cooler, etc.) may be connected to, disposed on or
otherwise associated with that fill syringe 52 (or other fill
reservoir) containing the thrombin-containing component and/or with
the component injector syringe 18 (or other injector) that contains
the thrombin-containing component. It will be appreciated that, for
other therapies, other types of temperature control or maintenance
apparatus (including any suitable heating and/or cooling apparatus)
may be used to provide a component substance that is warmed or
cooled to a desired temperature.
[0049] Also, in such cases, the platelet-containing component may
comprise a suspension of platelets (e.g., PRP is a suspension of
platelets in plasma). As such, it may be desirable or necessary to
maintain the platelets in a substantially homogenous suspension
until the time of injection. In such instances, the object is to
maintain the suspension of the platelets but not to agitate the PRP
to the point where the platelets are damaged or sheared. To
accomplish this, the entire injection device may be gently shaken
or moved by hand or by mechanical means between doses of the
therapy. Or, the device may optionally include an agitation device
80 for agitating (e.g., mixing, shaking, stirring, swirling,
moving, spinning, etc.) at least those portions of the device that
contain the platelet-containing component. For example, as seen in
the example of FIG. 6, an agitation device 80 comprising a small
vibrator 84 that is attached to the fill syringe 52 by an elastic
band 88, may be used to gently agitate PRP contained within fill
syringe 52 by vibrating the barrel of the syringe sufficiently to
maintain the PRP in a homogenous suspension.
[0050] It is to be further appreciated that the invention has been
described hereabove with reference to certain examples or
embodiments of the invention but that various additions, deletions,
alterations and modifications may be made to those examples and
embodiments without departing from the intended spirit and scope of
the invention. For example, any element or attribute of one
embodiment or example may be incorporated into or used with another
embodiment or example, unless to do so would render the embodiment
or example unsuitable for its intended use. Also, where the steps
of a method or process are described, listed or claimed in a
particular order, such steps may be performed in any other order
unless to do so would render the embodiment or example not novel,
obvious to a person of ordinary skill in the relevant art or
unsuitable for its intended use. All reasonable additions,
deletions, modifications and alterations are to be considered
equivalents of the described examples and embodiments and are to be
included within the scope of the following claims.
* * * * *